Klaus Ewe

Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD)

Hyporesponsiveness to a universe of bacterial and dietary antigens from the gut lumen is a hallmark of the intestinal immune system. Since hyperresponsiveness against these antigens might be associated with inflammation, we studied the immune response to the indigenous intestinal microflora in peripheral blood, inflamed and non‐inflamed human intestine. Lamina propria monocuclear cells (LPMC) isolated from inflamed intestine but not peripheral blood mononuclear cells (PBMC) of IBD patients with active inflammatory disease strongly proliferated after co‐culture with sonicates of bacteria from autologous intestine (BsA), Proliferation was inhibitable by anti‐MHC class II MoAb, suggesting that it was driven by antigen, LPMC from adjacent non‐inflamed intestinal areas of the same IBD patients and PBMC or LPMC isolated from non‐inflamed intestine of controls and patients with IBD in remission, in contrast, did not proliferate, PBMC or LPMC which had been tolerant to bacteria from autologous intestine, however, strongly proliferated after co‐culture with bacterial sonicates from heterologous intestine (BsH). This proliferation was associated with an expansion of CD8+ T cells, increased expression of activation markers on both CD4+ and CD8+ lymphocyte subsets, and production of IL‐12, interferon‐gamma (IFN‐γ), and IL‐10 protein. These results show that tolerance selectively exists to intestinal flora from autologous but not heterologous intestine, and that tolerance is broken in intestinal inflammation. This may be an important mechanism for the perpetuation of chronic IBD.

Bleeding after liver biopsy does not correlate with indices of peripheral coagulation

AbstractContraindications for percutaneous liver biopsy are often derived arbitrarily from coagulation status of peripheral blood, but no objective data are available on the duration of bleeding from the site of liver biopsy. “Liver bleeding time” (LBT) was measured after liver biopsy had been performed at laparoscopy in 200 consecutive patients using a 1.8-mm-diameter Menghini needle. LBT was then analyzed in relation to prothrombin time, platelet count, whole blood clot time, length of biopsy cylinder, and liver histopathology. There was no correlation among any of these variables. The average LBT was 4 min 37 sec±3 min 48 sec (sd). In 10 patients LBT was prolonged over 12 min

Fecal blood loss in patients with colonic polyps: a comparison of measurements with 51chromium-labeled erythrocytes and with the Haemoccult test

(\bar X \pm 2SD)

Inflammation does not decrease intraluminal pH in chronic inflammatory bowel disease.

, but their clotting indices were not different from those of other patients. Bleeding could be stopped easily by compression if necessary. This lack of correlation may be explained by the high concentration of clotting factors in hepatic parenchyma and by mechanical compression of the needle track by the elastic tissue in the liver. It is concluded that indices of coagulation in the peripheral blood used in this study are unreliable guides of the risk of bleeding after liver biopsy and, hence, are of limited value in determining contraindications to this procedure.

Gastric emptying of indigestible tablets in relation to composition and time of ingestion of meals studied by metal detector

BACKGROUND The role of azathioprine (AZA) in the treatment of active Crohns disease (CD) is still controversial. This study examined whether AZA combined with standard prednisolone therapy improved the therapeutic outcome compared with monotherapy with prednisolone. METHODS Forty-two patients with a Crohns Disease Activity Index (CDAI) of > 150 were randomized into two groups. Both received 60 mg of prednisolone daily in a tapering regimen to a maintenance dose of 10 mg. In addition, group 1 received 2.5 mg AZA/kg body wt and group 2 received a placebo over the whole study period of 4 months. RESULTS At the end of the trial, 16 of 21 patients (76%) in group 1 were in remission (CDAI < 150), compared with 8 of 21 (38%) in group 2 (P = 0.03). The CDAI in group 1 dropped from 290 +/- 97 (SD) to 72 +/- 84 and from 285 +/- 110 to 155 +/- 105 in group 2. The differences between activity indices in groups 1 and 2 became statistically significant after 8 weeks. The average prednisolone dose per day was 20.9 mg in group 1 and 26.7 mg in group 2 (P = 0.02). No major side effects were observed in this study. CONCLUSION The combination of prednisolone and AZA was superior to the treatment with prednisolone alone in active CD. Patients receiving AZA showed remission more frequently, more quickly, and with lower doses of prednisolone.

Effect of bisacodyl on intestinal electrolyte and water net transport and transit. Perfusion studies in men.

The quantitative determinations of fecal daily blood loss after intravenous administration of 51Cr-labeled erythrocytes in 44 patients with colonic polyps and in 11 controls were compared with the results of the daily performed Haemoccult test without dietary restrictions. A total of 642 stool specimens was analyzed for 51Cr loss and the Haemoccult test. The mean fecal daily blood loss in the 34 patients with adenomatous polyps of the descending colon and rectosigmoid was 1.36 +/- 0.14 ml/day (mean +/- SEM), in the 10 patients with polyps of the ascending and transverse colon it was 1.28 +/- 0.31 ml/day, and in the 11 controls 0.62 +/- 0.07 ml/day. There was no positive Haemoccult test in the controls. In fecal specimens from patients with polyps in the descending colon and rectosigmoid containing 2.0-3.99 ml blood/day, the Haemoccult-test was positive in 86%. Fecal specimens from patients with polyps in the ascending colon and transverse colon containing equal blood loss yielded a positive Haemoccult test result in 26%. Thus, the positivity of the Haemoccult test is determined by the fecal daily blood loss and the anatomic location of colonic bleeding sites.

Antibodies to cytoskeletal proteins in patients with Crohn's disease

It is widely accepted that glyceryl trinitrate (GTN) effectively dilates the smooth muscles of blood vessels. A similar effect has been postulated on the smooth muscles in the gastrointestinal tract. In this study the motility of the sphincter of Oddi and the common bile duct pressure as determined by endoscopic manometry was investigated in nine patients before and after sublingual application of 1.2 mg GTN (nitro group). Eight untreated patients served as controls. Three minutes after application of GTN the papillary contraction amplitude decreased from 69.3 +/- 4.3 mmHg to 36.8 +/- 5.1 mmHg (p less than 0.005) and the papillary baseline pressure fell from 8.9 +/- 0.6 mmHg to 2.9 +/- 0.2 mmHg (p less than 0.005) respectively. The contraction frequency in the nitro group and all motility parameters in the control group remained unchanged. These results indicate that GTN does not influence the sphincter of Oddi motility, but it relaxes very effectively the sphincter of Oddi muscle. Thus, GTN should be taken into account for the treatment of biliary colic. In our endoscopic unit GTN proved to be useful as premedication for endoscopic examinations, particularly for the removal of small and medium size common bile duct stones through the intact papilla.

Eflect of lactose, lactulose and bisacodyl on gastrointestinal transit studied by metal detector

Intestinal inflammation may influenceintraluminal pH. Profiles of the gastrointestinal pHwere evaluated in 15 patients with active Crohnsdisease of the ileocecal area. In addition, fivepatients with moderate (1) or severe (4) ulcerative colitiswere studied. Fifteen healthy subjects served ascontrols. Intraluminal pH of the different parts of thegastrointestinal tract was measured by a free-floating pH-sensitive telemetering capsule. A metalsphere was attached to the capsule for exactlocalization by a metal detector. Physiological patternsof pH were maintained throughout the gastrointestinaltract including the inflamed segments. Median pH inthe terminal ileum of the patients with Crohns diseasewas 7.5 vs 7.7 and in the rectum in ulcerative colitis7.8 vs 7.2 in the controls. In conclusion, intraluminal pH is not decreased by inflammatory changes inCrohns disease and ulcerative colitis, allowingeudragit-coated pH-controlled-release formulations ofmesalazine to dissolve in diseased areas also.